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O35240 (ASIC3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acid-sensing ion channel 3

Short name=ASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Dorsal root ASIC
Short name=DRASIC
Gene names
Name:Asic3
Synonyms:Accn3, Drasic
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length533 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties. Ref.7 Ref.9 Ref.14 Ref.18

Subunit structure

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with LIN7B, MAGI1 and GOPC By similarity. Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity. Ref.2 Ref.17 Ref.18

Subcellular location

Cytoplasm By similarity. Cell membrane; Multi-pass membrane protein By similarity. Note: In part cytoplasmic in cochlea cells By similarity. Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4. Ref.11 Ref.17 Ref.18

Tissue specificity

Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal chord and brain stem. Ref.1 Ref.3 Ref.5 Ref.11

Developmental stage

Expression is first detected at E15.5. Strongly expressed perinatally. Ref.12

Induction

Transcriptionally regulated by the proinflamatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs. Ref.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.13

Domain

The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1 By similarity.

Post-translational modification

Phosphorylated by PKA By similarity. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel. Ref.16

Miscellaneous

Potentiated by FMRFamide-related neuropeptides By similarity. Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdetection of chemical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of mechanical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of temperature stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from electronic annotation. Source: Ensembl

response to acidity

Inferred from direct assay Ref.1. Source: MGI

response to heat

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Inferred from direct assay Ref.1. Source: GOC

sodium ion transport

Inferred from direct assay Ref.1. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionPDZ domain binding

Inferred from mutant phenotype PubMed 16234233. Source: RGD

enterobactin transporter activity

Inferred from electronic annotation. Source: Ensembl

ligand-gated sodium channel activity

Inferred from direct assay Ref.1. Source: MGI

protein binding

Inferred from physical interaction PubMed 11872753PubMed 16234233Ref.18. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

InadlQ63ZW7-32EBI-982374,EBI-8158524From a different organism.
Slc9a3r1Q9JJ195EBI-982374,EBI-982391
Slc9a3r2Q920G22EBI-982374,EBI-982439
StomP541163EBI-982374,EBI-8004826From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 533533Acid-sensing ion channel 3
PRO_0000181303

Regions

Topological domain1 – 1919Cytoplasmic Potential
Transmembrane20 – 4021Helical; Potential
Topological domain41 – 435395Extracellular Potential
Transmembrane436 – 45621Helical; Potential
Topological domain457 – 53377Cytoplasmic Potential
Motif530 – 5334PDZ-binding By similarity

Sites

Site261Potassium ion selectivity and permeability

Amino acid modifications

Modified residue401Phosphothreonine; by PKC Probable
Modified residue5231Phosphoserine; by PKC Probable
Glycosylation1761N-linked (GlcNAc...) Potential
Glycosylation4001N-linked (GlcNAc...) Potential
Disulfide bond93 ↔ 187 By similarity
Disulfide bond165 ↔ 172 By similarity
Disulfide bond283 ↔ 372 By similarity
Disulfide bond317 ↔ 368 By similarity
Disulfide bond321 ↔ 366 By similarity
Disulfide bond330 ↔ 352 By similarity
Disulfide bond332 ↔ 344 By similarity

Experimental info

Mutagenesis201V → P: No effect on selectivity or channel function. Ref.4
Mutagenesis211F → S: Loss of channel function. Ref.4
Mutagenesis261T → K: Alters selectivity of the channel for sodium. No effect on channel function. Ref.4
Mutagenesis401T → G: Loss of regulation by PKC through PRKCABP; when associated with G-523. Ref.16
Mutagenesis5231S → G: Loss of regulation by PKC through PRKCABP; when associated with G-40. Ref.16

Sequences

Sequence LengthMass (Da)Tools
O35240 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 294B57322C74B3DC

FASTA53359,227
        10         20         30         40         50         60 
MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV LLSLAAFLYQ 

        70         80         90        100        110        120 
VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR SRLTPNDLHW AGTALLGLDP 

       130        140        150        160        170        180 
AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL YARAGHSLED MLLDCRYRGQ PCGPENFTVI 

       190        200        210        220        230        240 
FTRMGQCYTF NSGAHGAELL TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV 

       250        260        270        280        290        300 
QIHSQDEPPA IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP 

       310        320        330        340        350        360 
LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK DCASPALDAM 

       370        380        390        400        410        420 
LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN RSESYITENV LVLDIFFEAL 

       430        440        450        460        470        480 
NYEAVEQKAA YEVSELLGDI GGQMGLFIGA SLLTILEILD YLCEVFQDRV LGYFWNRRSA 

       490        500        510        520        530 
QKRSGNTLLQ EELNGHRTHV PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL 

« Hide

References

[1]"Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons."
Waldmann R., Bassilana F., de Weille J.R., Champigny G., Heurteaux C., Lazdunski M.
J. Biol. Chem. 272:20975-20978(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells."
Lingueglia E., de Weille J.R., Bassilana F., Heurteaux C., Sakai H., Waldmann R., Lazdunski M.
J. Biol. Chem. 272:29778-29783(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASIC1.
Strain: Wistar.
Tissue: Brain.
[3]"A sensory neuron-specific, proton-gated ion channel."
Chen C.-C., England S., Akopian A.N., Wood J.N.
Proc. Natl. Acad. Sci. U.S.A. 95:10240-10245(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[4]"The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore."
Coscoy S., de Weille J.R., Lingueglia E., Lazdunski M.
J. Biol. Chem. 274:10129-10132(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF VAL-20; PHE-21 AND THR-26.
[5]"Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+."
Babinski K., Catarsi S., Biagini G., Seguela P.
J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors."
Voilley N., de Weille J.R., Mamet J., Lazdunski M.
J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, INHIBITION BY DRUGS.
[7]"Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons."
Immke D.C., McCleskey E.W.
Nat. Neurosci. 4:869-870(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY LACTATE, FUNCTION.
[8]"Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF."
Catarsi S., Babinski K., Seguela P.
Neuropharmacology 41:592-600(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY NPFF.
[9]"Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons."
Sutherland S.P., Benson C.J., Adelman J.P., McCleskey E.W.
Proc. Natl. Acad. Sci. U.S.A. 98:711-716(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels."
Mamet J., Baron A., Lazdunski M., Voilley N.
J. Neurosci. 22:10662-10670(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system."
Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.
Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[12]"How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons."
Mamet J., Lazdunski M., Voilley N.
J. Biol. Chem. 278:48907-48913(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, INDUCTION BY NGFB.
[13]"Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade."
Immke D.C., McCleskey E.W.
Neuron 37:75-84(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY LACTATE AND CALCIUM.
[14]"Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability."
Deval E., Baron A., Lingueglia E., Mazarguil H., Zajac J.-M., Lazdunski M.
Neuropharmacology 44:662-671(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons."
Diochot S., Baron A., Rash L.D., Deval E., Escoubas P., Scarzello S., Salinas M., Lazdunski M.
EMBO J. 23:1516-1525(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY APETX2 TOXIN.
[16]"ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1."
Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M.
J. Biol. Chem. 279:19531-19539(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-40 AND SER-523, PHOSPHORYLATION AT THR-40 AND SER-523.
[17]"PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current."
Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.
J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DLG4, SUBCELLULAR LOCATION.
[18]"A stomatin dimer modulates the activity of acid-sensing ion channels."
Brand J., Smith E.S., Schwefel D., Lapatsina L., Poole K., Omerbasic D., Kozlenkov A., Behlke J., Lewin G.R., Daumke O.
EMBO J. 31:3635-3646(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STOM, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF013598 mRNA. Translation: AAB69328.1.
RefSeqNP_775158.1. NM_173135.1.
UniGeneRn.24225.

3D structure databases

ProteinModelPortalO35240.
SMRO35240. Positions 41-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-35759N.
IntActO35240. 4 interactions.
MINTMINT-1777886.
STRING10116.ENSRNOP00000011300.

Chemistry

BindingDBO35240.
ChEMBLCHEMBL5757.

Protein family/group databases

TCDB1.A.6.1.2. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSiteO35240.

Proteomic databases

PRIDEO35240.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000011300; ENSRNOP00000011300; ENSRNOG00000008380.
GeneID286920.
KEGGrno:286920.

Organism-specific databases

CTD9311.
RGD708578. Asic3.

Phylogenomic databases

eggNOGNOG262945.
GeneTreeENSGT00640000091217.
HOGENOMHOG000247010.
HOVERGENHBG004150.
InParanoidO35240.
KOK04830.
OMATECHMEC.
OrthoDBEOG72VH5P.
PhylomeDBO35240.
TreeFamTF330663.

Gene expression databases

GenevestigatorO35240.

Family and domain databases

InterProIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERPTHR11690. PTHR11690. 1 hit.
PfamPF00858. ASC. 1 hit.
[Graphical view]
PRINTSPR01078. AMINACHANNEL.
TIGRFAMsTIGR00859. ENaC. 1 hit.
PROSITEPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio625060.
PROO35240.

Entry information

Entry nameASIC3_RAT
AccessionPrimary (citable) accession number: O35240
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: January 1, 1998
Last modified: June 11, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families